Structure–function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination
Copyright policy )Structure–function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination
SignificanceThe sex-determining factor SRY is thought to function by up-regulating expression of its key target gene SRY-box 9 (SOX9) in pre-Sertoli cells of the developing gonads, but evidence for a transactivation domain is lacking for human SRY and is limited to in vitro evidence for mouse Sry. The latter is unusual in possessing a polyglutamine tract at its C terminus. We demonstrate, using a combination of biochemical, cell-based, and transgenic mouse assays, that this domain plays essential roles in both protein stabilization and transactivation ofSox9, and is required for male sex determination in mice. Our data indicate that mouse Sry has evolved a novel bifunctional module, revealing an unexpected level of plasticity of sex-determining mechanisms even among mammals.
- University of Hawaiʻi Sea Grant United States
- University of Queensland Australia
- National Oceanic and Atmospheric Administration United States
- University of Hawaii at Manoa United States
- University of Queensland Australia
Male, 570, Proteasome Endopeptidase Complex, Protein Denaturation, 572, Mice, Transgenic, Evolution, Molecular, Mice, Genes, Reporter, Pregnancy, Testis, Animals, Genes, sry, Sequence Deletion, Y chromosome, Protein Stability, SOX9 Transcription Factor, TESCO, Sex Determination Processes, Peptide Fragments, Sex-Determining Region Y Protein, Protein Structure, Tertiary, Mutagenesis, Sex development, 1000 General, Female, Peptides
Male, 570, Proteasome Endopeptidase Complex, Protein Denaturation, 572, Mice, Transgenic, Evolution, Molecular, Mice, Genes, Reporter, Pregnancy, Testis, Animals, Genes, sry, Sequence Deletion, Y chromosome, Protein Stability, SOX9 Transcription Factor, TESCO, Sex Determination Processes, Peptide Fragments, Sex-Determining Region Y Protein, Protein Structure, Tertiary, Mutagenesis, Sex development, 1000 General, Female, Peptides
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